Lecture 19- Tuberculosis

Question 1

What is TB caused by?

Answer 1

Mycobacterium tuberculosis

• Aerobic
• Acid and alcohol fast bacilli
• Slow growing

Question 2

Demographics and risk factors

Answer 2

• Non-UK born/recent migraines
  
  • South Asia 54%
  • Sub-Saharan Africa 29%
• HIV
• Immunosuppressed
• Homeless
• Drug users, prison
• Close contacts
• Young adults (also higher incidence in elderly)

Question 3

How can we stain for tuberculosis?

Answer 3

Sputum smear stained with Ziehl-Nielsen method

Takes 2-6 weeks to grow colonies

–> cant tell if TB alive or dead

Question 4

in the UK TB is mainly found in

Answer 4

non-UK born

Question 5

How does TB transmit from person to person?

Answer 5

• infected droplets from coughing and sneezing
• Infectious dose 1-10 bacilli
• Contagious, but not easy to acquire infection
• Need prolonged exposure to facilitate transmission (at least 8-hours /day up to 6 months)
  
  • Households
  • Prisons
  • School
• Lots of factors need to be fulfilled for transmission

Question 6

Where is the most common site of pulmonary TB?

Answer 6

Right lung apex as high pO2 in these areas compared to the rest of the lungs

Question 7

pathogenesis of TB

Answer 7

• Alveolar macrophages phagocytose MTB but cannot kill them as cell wall lipids of MTB block fusion of phagosome and lysosome
• Macrophages initiate cell mediated immunity so activated macrophages can come and kill MTB, takes about 6 weeks
• Granulomatous reaction from macrophages

Question 8

primary complex (Ghons focus and draining lymph node) can have 3 outcomes

Answer 8

1. Active primary disease (5%)
2. Initial containment of infections
   
   • Heals/self cure
   • Post primary infection TB

Question 9

What could cause a latent TB infection to reactivate?

Answer 9

• HIV
• Chemotherapy
• Malnutrition
• Old age
• corticosteroids
• immunosuppressive therapy e.g. organ transplant

Question 10

What is the likelihood of someone being infected with TB actually developing the active disease?

Answer 10

10% lifetime risk

• 5% develop primary TB at initial infection when primary complex does not heal
• 5% develop post primary TB up to 60 years after initial infection

Question 11

TB with symptoms=

Answer 11

infectious

Question 12

Primary TB become symptomatic after first exposure to TB

Answer 12

• Ghon focus/complex
• Limited by CMI
• Usually asymptomatic
• Rare allergic reactions include erythema nodosum
• Occasionally symptomatic and can also disseminate
• i.e. military and extra pulmonary

Question 13

The general symptoms of TB disease include

Answer 13

Unexplained weight loss

Loss of appetite

Night sweats

Fever

Fatigue

Chills

Question 14

The symptoms of TB of the lungs include

Answer 14

Coughing for 3 weeks or longer

Hemoptysis (coughing up blood)

Chest pain

Question 15

Post-primary TB

Answer 15

• reactivation by exogenous re-infection
  
  • latent –> disease
• much more symptomatic
• >5 years after primary infection
• 5-10% risk per lifetime
• Clinical presentation
  
  • Pulmonary or extra-pulmonary

Question 17

how can we test for latent infection

Answer 17

IGRA (QuantiFERON)

Tuberculin skin test

Question 18

IGRA (QuantiFERON)

Answer 18

MTB antigens can make the body produce interferon gamma. Lymphocytes from the patient are cultured with MTB antigens and if T lymphocytes have been exposed before they will produce interferon gamma. The MTB antigen is not present in BCG or atypical mycobacteria so can distinguish latent from BCG vaccine

Question 19

Tuberculin Skin Test:

Answer 19

Protein from MTB injected intradermally. Skin reaction 48-72 hours later indicates previous TB exposure, type IV hypersensitivity reaction to MTB

indicates sensitive T cells

Question 20

positives and negatives of tubercukin skin test

Answer 20

Positives

• Cheap
• Lab infrastructure not required
• Evidence to support ability to predict active disease in those that are latently infected

Negatives

• False positives- BCG non TB
• False negatives (immunocompromised i.e. HIV/drugs/ advanced disease)

Question 22

positives and ngeatives of IGRA

Answer 22

Advantages

• Antigens are only found in M. tb (not in BCG)

Disadvantages

• Cannot distinguish latent and active TB
• Similar problems with sensitivity and specificity

Question 23

What are some of the changes a patient may have with post primary TB?

Answer 23

• Cavity formation: liquefaction of caseous material. Fibrous tissue usually around periphery of lesions
• Haemorraghe: extension of caseous process into vessels. leads to haemoptysis
• Spread to rest of lung
• Pleural effusion: seeding of TB into pleura or hypersensitivity
• Miliary TB: rupture of caseous pulomnary focus into blood vessel so widespread dissemination through body

Question 24

What are some sites of extrapulmonary TB?

Answer 24

Miliary TB

• Bacteria spreading through the blood stream –> widespread infection
• Lymph nodes
• Bones
• Joints
• CNS
• GI tract
• Urinary tract
• brain (tb meningitis)

Question 25

when does milliary tb occur

Answer 25

* Either during primary infection or during reactivation * Lungs are always involved- but few respiratory symptoms * Fever, very unwell, dry cough * Often multiple organs involved * Other organ involvement is variable * Headaches suggest meningeal involvement * Pericardial- pleural effusions small * Ascites may be present * Retinal involvement (Choroid tubercles seen)

Question 26

What are some clinical features of pulmonary TB?

Answer 26

- Gradual onset over weeks or months - Tiredness - Malaise - Weight loss - Fever - Sweats - Cough with haemoptysis - Can be asymptomatic even when CXR abnormal - Crackles may be present - Signs of pleural effusion or fibrosis

Question 27

What does a CXR of TB look like?

Answer 27

Ghons focus ## Footnote - Patchy solid lesions - Cavity solid lesions - Streaky fibrosis - Flecks of calcification

Question 28

How do we diagnose active TB?

Answer 28

* **radiology most important** * microscopy * **culture** * **histology**

Question 29

**TB microscopy**

Answer 29

* Rapid and cheap test * **Zeal-neelson (ZN)stain used (acid-fast)** * Pink bacilli * For test to be positive = need at least 5000 bacilli * Smear positive case * Cannot differentiate MTB from NTM * Cannot differentiate live and dead organisms

Question 30

why doesnt the TB gram stain

Answer 30

encapsulated

Question 31

**TB culture- second most important** *

Answer 31

* Remains gold standard for TB diagnostics * One of the most sensitive methods for detecting mycobacteria * Solid and liquid culture system * Has improve automated culture technology * Allows identification and susceptibility testing

Question 32

types of TB culture

Answer 32

**Lowenstein jensen slopes** **Automated TB culture** **Additional test**

Question 33

**Lowenstein jensen slopes**

Answer 33

* Bacilli takes a long time to grow in this (2-6 weeks) * Will need to be sent for microscopy identification

Question 34

**Automated TB culture**

Answer 34

* Liquid culture medium * Sample goes into automated machine * **Much more sensitive than solid cultures** * Detect growth of TB bacilli by measuring the change in pH (CO2 conc) * **Can detect growth much earlier (10-14 days)**

Question 35

additional tests

Answer 35

* Nucleic acid amplification test (NAAT) * Rapid diagnosis of smear positive * Drug resistance mutations * GWAS

Question 36

What does TB look like using histology?

Answer 36

- Granuloma with central caseous necrosis (cheese) surround by epitheliod macrophages, langhans giant cells and lymphocytes

Question 37

How do we treat TB?

Answer 37

- Rifampicin (red urine) - Isoniazid (INAH) - Pyrazinamide - Ethambutol All 4 drugs for 2 months and then just R and INAH for a further 4 months. Give pyridoxine with INAH to stop peripheral nerve damage **low compliance**

Question 38

multidrug therapy

Answer 38

Question 39

Why do we give 4 drugs for TB?

Answer 39

One drug would allow selection of resistant strains, less likely to be resistant to all three drugs pts at risk- those not taking the medication

Question 40

What should you do if you diagnose a patient with TB?

Answer 40

- Isolate and notify public health - PPE - Contact trace and vaccinate

Question 41

difference between latent and active disease

Answer 41

Question 42

adverse affect of drugs

Answer 42

Question 43

What are some extra-pulmonary signs of miliary TB?

Answer 43

- Headaches as meningeal involvement - Pericardial and pleural effusions - Retinal involvement - Ascites

Question 44

**Offer prophylactic drugs to pts with**

Answer 44

**latent TB – to kill dormant TB- reduce number of people with active disease**

Question 45

**BCG- Bacilli Calmette-Guerin vaccine**

Answer 45

* Live attenuated M.bovis strain * Given to babies in high prevalence communities * 70-80% effectiveness in preventing severe childhood TB * Protection wanes * Little evidence in adults * Not part of routine childhood vaccination schedule only given to neonates/ infants / older children thought to have an increased risk of coming into contact with TB * Other indication * New entrants from high-risk areas * Health workers * Close contacts of active resp TB * Other groups- ref green book * Always consider HIV testing where appropriate before giving BCG

Question 46

Ghon focus

Answer 46

ghon focus- granuloma with associated WBC ghon comples- ghon focus with associated lymph node

Question 47

granuloma formation

Answer 47

* Granuloma * A collection of epithelioid histiocytes (macrophages) with surrounding lymphocytes May also see giant cells within granuloma